Ion channels and solute transporters are essential players in a diverse array of cellular, organ and whole organism functions. Defining the molecular structure, regulation and physiological roles of these proteins represents the leading edge of the field of membrane transport biology. In the wake of genome sequencing, two new questions in this field have emerged: What are the physiological functions of an identified ion channel or transporter gene? What are the genes in an organism's genetic blueprint responsible for a given ion channel or transporter mediated physiological process. Answering these questions presents enormous intellectual and technical challenges that have resulted in a paradigm shift in investigation strategies. It has become essential to utilize simpler, genetically and experimentally more manipulatable organisms to understand fully the genetic and molecular basis of complex physiological process and human pathophysiology. The remarkable conservation of structure and function demonstrated by genome sequencing underscores the necessity of using "model organisms" to address basic biological questions. The nematode Caenorhabditis elegans offers tremendous experimental advantages for studies of membrane transport physiology. These advantages include a fully sequenced genome, molecular and cellular manipulability a rapid lifecycle, and the ability to carry out powerful genetic analysis of physiological processes. This Program, exploit the experimental power of C. elegans to define fundamental aspects of CIC anion channel, acetylcholine receptor and neurotransmitter transporter function, regulation, and structure. The scientific questions posed by Program investigators are relevant to the biology of all organisms and are not tractable using other eukaryotic experimental systems.